3-169926688-G-C

Variant names:

• chr3-169926688-G-C
• NM_001304366.2:c.426G>C

Variant summary

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

The NM_001304366.2(SAMD7):​c.426G>C​(p.Arg142Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SAMD7 NM_001304366.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.426G>C	p.Arg142Ser	missense	Exon 6 of 9	NP_001291295.1	Q7Z3H4
	SAMD7	NM_182610.4		c.426G>C	p.Arg142Ser	missense	Exon 6 of 9	NP_872416.1	Q7Z3H4
	SAMD7	NR_130713.2		n.905G>C		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.426G>C	p.Arg142Ser	missense	Exon 6 of 9	ENSP00000334668.3	Q7Z3H4
	SAMD7	ENST00000428432.6	TSL:1	c.426G>C	p.Arg142Ser	missense	Exon 6 of 9	ENSP00000391299.2	Q7Z3H4
	SAMD7	ENST00000487910.1	TSL:1	n.*242G>C		non_coding_transcript_exon	Exon 6 of 9	ENSP00000420460.1	F8WDF1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

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	0.31
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.0
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.41
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.029	D
Polyphen		0.99	D
Vest4		0.58
MutPred		0.31		Loss of methylation at R142 (P = 0.0143)
MVP		0.84
MPC		0.37
ClinPred		0.92	D
GERP RS		1.9
Varity_R		0.14
gMVP		0.61
Mutation Taster		=38/62	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: chr3-169644476;