Genetic Variant SAMD7:p.Met165Ile (chr3-169926757-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001304366.2(SAMD7):c.495G>A(p.Met165Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SAMD7
NM_001304366.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.40

Publications

0 publications found

Variant links:

Genes affected

SAMD7 (HGNC:25394): (sterile alpha motif domain containing 7) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SAMD7 Gene-Disease associations (from GenCC):

macular dystrophy with or without cone dysfunction
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics

SAMD7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05747333).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304366.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAMD7	NM_001304366.2	MANE Select	c.495G>A	p.Met165Ile	missense	Exon 6 of 9	NP_001291295.1	Q7Z3H4
SAMD7	NM_182610.4		c.495G>A	p.Met165Ile	missense	Exon 6 of 9	NP_872416.1	Q7Z3H4
SAMD7	NR_130713.2		n.974G>A		non_coding_transcript_exon	Exon 7 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAMD7	ENST00000335556.7	TSL:1 MANE Select	c.495G>A	p.Met165Ile	missense	Exon 6 of 9	ENSP00000334668.3	Q7Z3H4
SAMD7	ENST00000428432.6	TSL:1	c.495G>A	p.Met165Ile	missense	Exon 6 of 9	ENSP00000391299.2	Q7Z3H4
SAMD7	ENST00000487910.1	TSL:1	n.*311G>A		non_coding_transcript_exon	Exon 6 of 9	ENSP00000420460.1	F8WDF1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151972

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251416

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151972

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41382

American (AMR)

AF:

0.00

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.8

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.0017

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.46

M_CAP

Benign

0.0058

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

PhyloP100

1.4

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.89

REVEL

Benign

0.047

Sift

Benign

0.69

Sift4G

Benign

0.90

Polyphen

0.0010

Vest4

0.15

MutPred

0.37

Loss of disorder (P = 0.0384)

MVP

0.19

MPC

0.15

ClinPred

0.027

GERP RS

0.77

Varity_R

0.058

gMVP

0.074

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over