3-169925110-A-T

Variant names:

• chr3-169925110-A-T
• NM_001304366.2:c.264A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001304366.2(SAMD7):​c.264A>T​(p.Glu88Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SAMD7 NM_001304366.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.363

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25252515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD7	NM_001304366.2	c.264A>T	p.Glu88Asp	missense_variant	Exon 5 of 9	ENST00000335556.7	NP_001291295.1
SAMD7	NM_182610.4	c.264A>T	p.Glu88Asp	missense_variant	Exon 5 of 9		NP_872416.1
SAMD7	NR_130713.2	n.630A>T		non_coding_transcript_exon_variant	Exon 5 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD7	ENST00000335556.7	c.264A>T	p.Glu88Asp	missense_variant	Exon 5 of 9	1	NM_001304366.2	ENSP00000334668.3
SAMD7	ENST00000428432.6	c.264A>T	p.Glu88Asp	missense_variant	Exon 5 of 9	1		ENSP00000391299.2
SAMD7	ENST00000487910.1	n.264A>T		non_coding_transcript_exon_variant	Exon 4 of 9	1		ENSP00000420460.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459274 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725696

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.264A>T (p.E88D) alteration is located in exon 5 (coding exon 3) of the SAMD7 gene. This alteration results from a A to T substitution at nucleotide position 264, causing the glutamic acid (E) at amino acid position 88 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-0.090
Eigen_PC	Benign	-0.081
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.66	.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.067
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.049	D;D
Polyphen		0.61	P;P
Vest4		0.39
MutPred		0.39		Loss of MoRF binding (P = 0.1442);Loss of MoRF binding (P = 0.1442);
MVP		0.57
MPC		0.17
ClinPred		0.91	D
GERP RS		-0.19
Varity_R		0.27
gMVP		0.49

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-169642898;