chr3-169926672-C-A

Variant names:

• chr3-169926672-C-A
• NM_001304366.2:c.410C>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.410C>A​(p.Ala137Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SAMD7 NM_001304366.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.817
• 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=0.19198292).

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.410C>A	p.Ala137Asp	missense	Exon 6 of 9	NP_001291295.1	Q7Z3H4
	SAMD7	NM_182610.4		c.410C>A	p.Ala137Asp	missense	Exon 6 of 9	NP_872416.1	Q7Z3H4
	SAMD7	NR_130713.2		n.889C>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.410C>A	p.Ala137Asp	missense	Exon 6 of 9	ENSP00000334668.3	Q7Z3H4
	SAMD7	ENST00000428432.6	TSL:1	c.410C>A	p.Ala137Asp	missense	Exon 6 of 9	ENSP00000391299.2	Q7Z3H4
	SAMD7	ENST00000487910.1	TSL:1	n.*226C>A		non_coding_transcript_exon	Exon 6 of 9	ENSP00000420460.1	F8WDF1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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: 53416

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

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

GnomAD4 genome Cov.: 31

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	0.21
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.82
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.18
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.049	D
Polyphen		0.97	D
Vest4		0.36
MutPred		0.29		Gain of relative solvent accessibility (P = 0.0249)
MVP		0.59
MPC		0.65
ClinPred		0.83	D
GERP RS		4.1
Varity_R		0.11
gMVP		0.45
Mutation Taster		=98/2	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

hg19: chr3-169644460; COSMIC: COSV104649836;