3-169926629-G-A

Variant names:

• chr3-169926629-G-A
• rs745698017
• NM_001304366.2:c.367G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001304366.2(SAMD7):​c.367G>A​(p.Gly123Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 0.0000021 (0 hom.)
• Consequence: SAMD7 NM_001304366.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.26
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19395691).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD7	NM_001304366.2	MANE Select	c.367G>A	p.Gly123Arg	missense	Exon 6 of 9	NP_001291295.1	Q7Z3H4
	SAMD7	NM_182610.4		c.367G>A	p.Gly123Arg	missense	Exon 6 of 9	NP_872416.1	Q7Z3H4
	SAMD7	NR_130713.2		n.846G>A		non_coding_transcript_exon	Exon 7 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD7	ENST00000335556.7	TSL:1 MANE Select	c.367G>A	p.Gly123Arg	missense	Exon 6 of 9	ENSP00000334668.3	Q7Z3H4
	SAMD7	ENST00000428432.6	TSL:1	c.367G>A	p.Gly123Arg	missense	Exon 6 of 9	ENSP00000391299.2	Q7Z3H4
	SAMD7	ENST00000487910.1	TSL:1	n.*183G>A		non_coding_transcript_exon	Exon 6 of 9	ENSP00000420460.1	F8WDF1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152040 Hom.: 0 Cov.: 31

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

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461752 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727178

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111926

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152040 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74280

African (AFR) AF: 0.0000242 AC: 1 AN: 41368

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-0.091
Eigen_PC	Benign	-0.047
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.3
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.15
Sift	Benign	0.12	T
Sift4G	Benign	0.088	T
Polyphen		0.25	B
Vest4		0.25
MutPred		0.52		Gain of MoRF binding (P = 0.0115)
MVP		0.59
MPC		0.21
ClinPred		0.58	D
GERP RS		5.3
Varity_R		0.072
gMVP		0.39
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs745698017; hg19: chr3-169644417; COSMIC: COSV59418780;