3-169919505-G-A

Variant names:

• chr3-169919505-G-A
• rs200767220
• NM_001304366.2:c.7G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001304366.2(SAMD7):​c.7G>A​(p.Val3Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SAMD7 NM_001304366.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.364
• 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: 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=0.07606056).
• BP6: Variant 3-169919505-G-A is Benign according to our data. Variant chr3-169919505-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2612321.Status of the report is criteria_provided_single_submitter, 1 stars.

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.7G>A	p.Val3Met	missense	Exon 3 of 9	NP_001291295.1	Q7Z3H4
	SAMD7	NM_182610.4		c.7G>A	p.Val3Met	missense	Exon 3 of 9	NP_872416.1	Q7Z3H4
	SAMD7	NR_130713.2		n.373G>A		non_coding_transcript_exon	Exon 3 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD7	ENST00000335556.7	TSL:1 MANE Select	c.7G>A	p.Val3Met	missense	Exon 3 of 9	ENSP00000334668.3	Q7Z3H4
	SAMD7	ENST00000428432.6	TSL:1	c.7G>A	p.Val3Met	missense	Exon 3 of 9	ENSP00000391299.2	Q7Z3H4
	SAMD7	ENST00000487910.1	TSL:1	n.7G>A		non_coding_transcript_exon	Exon 2 of 9	ENSP00000420460.1	F8WDF1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.2
DANN	Benign	0.21
DEOGEN2	Benign	0.00034	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.38	N
PhyloP100		0.36
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.027
Sift	Benign	0.43	T
Sift4G	Benign	0.39	T
Polyphen		0.20	B
Vest4		0.17
MutPred		0.086		Gain of glycosylation at P5 (P = 0.0986)
MVP		0.31
MPC		0.14
ClinPred		0.10	T
GERP RS		-1.2
Varity_R		0.027
gMVP		0.14
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs200767220; hg19: chr3-169637293;