2-27581247-C-T

Variant names:

• chr2-27581247-C-T
• rs13392197
• NM_032266.5:c.14887C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_032266.5(SPATA31H1):​c.14887C>T​(p.His4963Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,614,244 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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: 𝑓 0.0098 (26 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (28 hom.)
• Consequence: SPATA31H1 NM_032266.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

Genes affected

SPATA31H1 (HGNC:25275): (SPATA31 subfamily H member 1) Located in extracellular exosome and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003415078).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00977 (1489/152350) while in subpopulation AFR AF= 0.033 (1374/41576). AF 95% confidence interval is 0.0316. There are 26 homozygotes in gnomad4. There are 741 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31H1	NM_032266.5	c.14887C>T	p.His4963Tyr	missense_variant	Exon 5 of 5	ENST00000447166.3	NP_115642.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2orf16	ENST00000447166.3	c.14887C>T	p.His4963Tyr	missense_variant	Exon 5 of 5	3	NM_032266.5	ENSP00000403181.2

Frequencies

GnomAD3 genomes AF: 0.00972 AC: 1480 AN: 152232 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0329

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00269 AC: 671 AN: 249460 Hom.: 15 AF XY: 0.00222 AC XY: 300 AN XY: 135338

Gnomad AFR exome AF: 0.0339

Gnomad AMR exome AF: 0.00269

Gnomad ASJ exome AF: 0.000795

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000300

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00115 AC: 1684 AN: 1461894 Hom.: 28 Cov.: 60 AF XY: 0.00103 AC XY: 749 AN XY: 727248

Gnomad4 AFR exome AF: 0.0341

Gnomad4 AMR exome AF: 0.00268

Gnomad4 ASJ exome AF: 0.000536

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000206

Gnomad4 OTH exome AF: 0.00262

GnomAD4 genome AF: 0.00977 AC: 1489 AN: 152350 Hom.: 26 Cov.: 32 AF XY: 0.00995 AC XY: 741 AN XY: 74504

Gnomad4 AFR AF: 0.0330

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000367

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00221 Hom.: 12

Bravo AF: 0.0107

ESP6500AA AF: 0.0344 AC: 130

ESP6500EA AF: 0.000365 AC: 3

ExAC AF: 0.00301 AC: 364

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.029
DANN	Benign	0.61
DEOGEN2	Benign	0.0018	.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.35	T;T
MetaRNN	Benign	0.0034	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.4	.;L
PROVEAN	Benign	-1.2	.;N
REVEL	Benign	0.025
Sift	Benign	0.36	.;T
Sift4G	Benign	0.75	.;T
Polyphen		0.0010	.;B
Vest4		0.075
MVP		0.040
MPC		0.099
ClinPred		0.017	T
GERP RS		-5.8
Varity_R		0.035
gMVP		0.029

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: rs13392197; hg19: chr2-27804114;