NM_001304366.2:c.992A>T

Variant names:

• chr3-169928529-A-T
• NM_001304366.2:c.992A>T

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_001304366.2(SAMD7):​c.992A>T​(p.Asp331Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SAMD7 NM_001304366.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.64
• 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: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.931
• PP5: Variant 3-169928529-A-T is Pathogenic according to our data. Variant chr3-169928529-A-T is described in ClinVar as Pathogenic. ClinVar VariationId is 3062153.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD7	NM_001304366.2	c.992A>T	p.Asp331Val	missense_variant	Exon 7 of 9	ENST00000335556.7	NP_001291295.1
SAMD7	NM_182610.4	c.992A>T	p.Asp331Val	missense_variant	Exon 7 of 9		NP_872416.1
SAMD7	NR_130713.2	n.1471A>T		non_coding_transcript_exon_variant	Exon 8 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD7	ENST00000335556.7	c.992A>T	p.Asp331Val	missense_variant	Exon 7 of 9	1	NM_001304366.2	ENSP00000334668.3
SAMD7	ENST00000428432.6	c.992A>T	p.Asp331Val	missense_variant	Exon 7 of 9	1		ENSP00000391299.2
SAMD7	ENST00000487910.1	n.*808A>T		non_coding_transcript_exon_variant	Exon 7 of 9	1		ENSP00000420460.1
SAMD7	ENST00000487910.1	n.*808A>T		3_prime_UTR_variant	Exon 7 of 9	1		ENSP00000420460.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

MACULAR DYSTROPHY WITH CONE DYSFUNCTION Pathogenic:1

Mar 19, 2024

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	.;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Pathogenic	3.1	M;M
PhyloP100		8.6
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-8.8	D;D
REVEL	Pathogenic	0.74
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.96
MutPred		0.68		Loss of ubiquitination at K326 (P = 0.0896);Loss of ubiquitination at K326 (P = 0.0896);
MVP		0.82
MPC		0.74
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.89
gMVP		0.71
Mutation Taster		=32/68	disease causing

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

hg19: chr3-169646317;