rs2193595

Variant names:

• chr14-77378778-A-G
• rs2193595
• NM_001010860.4:c.1360A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010860.4(SAMD15):​c.1360A>G​(p.Lys454Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,611,202 control chromosomes in the GnomAD database, including 191,651 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.56 (26383 hom., cov: 33)
  • Exomes 𝑓: 0.47 (165268 hom.)
• Consequence: SAMD15 NM_001010860.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861

Genes affected

SAMD15 (HGNC:18631): (sterile alpha motif domain containing 15)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1498308E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD15	NM_001010860.4	c.1360A>G	p.Lys454Glu	missense_variant	Exon 1 of 3	ENST00000216471.5	NP_001010860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD15	ENST00000216471.5	c.1360A>G	p.Lys454Glu	missense_variant	Exon 1 of 3	2	NM_001010860.4	ENSP00000216471.4
SAMD15	ENST00000533095.2	c.-69-1605A>G		intron_variant	Intron 1 of 2	5		ENSP00000450941.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85080 AN: 152024 Hom.: 26339 Cov.: 33

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.0850

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.550

GnomAD3 exomes AF: 0.472 AC: 117586 AN: 248956 Hom.: 30394 AF XY: 0.472 AC XY: 63567 AN XY: 134552

Gnomad AFR exome AF: 0.836

Gnomad AMR exome AF: 0.475

Gnomad ASJ exome AF: 0.493

Gnomad EAS exome AF: 0.0769

Gnomad SAS exome AF: 0.513

Gnomad FIN exome AF: 0.468

Gnomad NFE exome AF: 0.471

Gnomad OTH exome AF: 0.483

GnomAD4 exome AF: 0.467 AC: 680851 AN: 1459060 Hom.: 165268 Cov.: 37 AF XY: 0.469 AC XY: 340082 AN XY: 725828

Gnomad4 AFR exome AF: 0.844

Gnomad4 AMR exome AF: 0.473

Gnomad4 ASJ exome AF: 0.494

Gnomad4 EAS exome AF: 0.0689

Gnomad4 SAS exome AF: 0.517

Gnomad4 FIN exome AF: 0.463

Gnomad4 NFE exome AF: 0.464

Gnomad4 OTH exome AF: 0.479

GnomAD4 genome AF: 0.560 AC: 85178 AN: 152142 Hom.: 26383 Cov.: 33 AF XY: 0.555 AC XY: 41256 AN XY: 74382

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.0850

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.544

Alfa AF: 0.486 Hom.: 45040

Bravo AF: 0.570

TwinsUK AF: 0.448 AC: 1660

ALSPAC AF: 0.467 AC: 1798

ESP6500AA AF: 0.823 AC: 3626

ESP6500EA AF: 0.468 AC: 4023

ExAC AF: 0.482 AC: 58516

Asia WGS AF: 0.316 AC: 1102 AN: 3478

EpiCase AF: 0.489

EpiControl AF: 0.487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.18
DANN	Benign	0.46
DEOGEN2	Benign	0.00092	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0068	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.021
Sift	Benign	0.50	T
Sift4G	Benign	0.94	T
Polyphen		0.0	B
Vest4		0.011
MPC		0.10
ClinPred		0.0041	T
GERP RS		-2.4
Varity_R		0.041
gMVP		0.025

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

LitVar

Other links and lift over

dbSNP: rs2193595; hg19: chr14-77845121; COSMIC: COSV53625817; COSMIC: COSV53625817;