Genetic Variant SAMD7:p.Pro217Leu (chr3-169926912-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001304366.2(SAMD7):c.650C>T(p.Pro217Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

SAMD7
NM_001304366.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.02

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07760337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD7	NM_001304366.2 link	c.650C>T	p.Pro217Leu	missense_variant	Exon 6 of 9	ENST00000335556.7	NP_001291295.1	Q7Z3H4
SAMD7	NM_182610.4 link	c.650C>T	p.Pro217Leu	missense_variant	Exon 6 of 9		NP_872416.1	Q7Z3H4
SAMD7	NR_130713.2 link	n.1129C>T		non_coding_transcript_exon_variant	Exon 7 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SAMD7	ENST00000335556.7 link	c.650C>T	p.Pro217Leu	missense_variant	Exon 6 of 9	1	NM_001304366.2	ENSP00000334668.3	Q7Z3H4
SAMD7	ENST00000428432.6 link	c.650C>T	p.Pro217Leu	missense_variant	Exon 6 of 9	1		ENSP00000391299.2	Q7Z3H4
SAMD7	ENST00000487910.1 link	n.*466C>T		non_coding_transcript_exon_variant	Exon 6 of 9	1		ENSP00000420460.1	F8WDF1
SAMD7	ENST00000487910.1 link	n.*466C>T		3_prime_UTR_variant	Exon 6 of 9	1		ENSP00000420460.1	F8WDF1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251426

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135908

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 SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151888

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74144

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.650C>T (p.P217L) alteration is located in exon 6 (coding exon 4) of the SAMD7 gene. This alteration results from a C to T substitution at nucleotide position 650, causing the proline (P) at amino acid position 217 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.57

DEOGEN2

Benign

0.0052

T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.60

.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.078

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.045

Sift

Benign

0.14

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.062

B;B

Vest4

0.16

MutPred

0.24

Gain of relative solvent accessibility (P = 0.0999);Gain of relative solvent accessibility (P = 0.0999);

MVP

0.54

MPC

0.16

ClinPred

0.069

GERP RS

5.3

Varity_R

0.077

gMVP

0.078

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over