6-28329536-T-A

Variant names:

• chr6-28329536-T-A
• rs853678
• NM_030899.5:c.148A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030899.5(ZSCAN31):​c.148A>T​(p.Thr50Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,613,804 control chromosomes in the GnomAD database, including 22,147 homozygotes. 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: 𝑓 0.19 (3639 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18508 hom.)
• Consequence: ZSCAN31 NM_030899.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.779
• Publications: 36 publications found

Genes affected

ZSCAN31 (HGNC:14097): (zinc finger and SCAN domain containing 31) This gene encodes a protein containing multiple C2H2-type zinc finger motifs. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ENSG00000294464 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0044205785).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030899.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN31	NM_030899.5	MANE Select	c.148A>T	p.Thr50Ser	missense	Exon 2 of 4	NP_112161.3
	ZSCAN31	NM_001135215.1		c.148A>T	p.Thr50Ser	missense	Exon 6 of 8	NP_001128687.1
	ZSCAN31	NM_001135216.1		c.148A>T	p.Thr50Ser	missense	Exon 2 of 4	NP_001128688.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN31	ENST00000344279.11	TSL:1 MANE Select	c.148A>T	p.Thr50Ser	missense	Exon 2 of 4	ENSP00000345339.6
	ZSCAN31	ENST00000396838.6	TSL:1	c.148A>T	p.Thr50Ser	missense	Exon 6 of 8	ENSP00000380050.2
	ZSCAN31	ENST00000439158.5	TSL:1	c.148A>T	p.Thr50Ser	missense	Exon 2 of 4	ENSP00000413705.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29206 AN: 151796 Hom.: 3629 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0925

Gnomad FIN AF: 0.0565

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.180

GnomAD2 exomes AF: 0.138 AC: 34781 AN: 251452 AF XY: 0.133

Gnomad AFR exome AF: 0.358

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.128

Gnomad FIN exome AF: 0.0607

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.152 AC: 221882 AN: 1461890 Hom.: 18508 Cov.: 32 AF XY: 0.149 AC XY: 108269 AN XY: 727244

African (AFR) AF: 0.360 AC: 12059 AN: 33478

American (AMR) AF: 0.140 AC: 6266 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 3364 AN: 26136

East Asian (EAS) AF: 0.152 AC: 6030 AN: 39700

South Asian (SAS) AF: 0.0947 AC: 8166 AN: 86258

European-Finnish (FIN) AF: 0.0629 AC: 3361 AN: 53420

Middle Eastern (MID) AF: 0.107 AC: 619 AN: 5768

European-Non Finnish (NFE) AF: 0.156 AC: 172953 AN: 1112010

Other (OTH) AF: 0.150 AC: 9064 AN: 60396

GnomAD4 genome AF: 0.192 AC: 29233 AN: 151914 Hom.: 3639 Cov.: 32 AF XY: 0.185 AC XY: 13707 AN XY: 74286

African (AFR) AF: 0.348 AC: 14408 AN: 41384

American (AMR) AF: 0.165 AC: 2511 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3468

East Asian (EAS) AF: 0.127 AC: 656 AN: 5152

South Asian (SAS) AF: 0.0928 AC: 446 AN: 4808

European-Finnish (FIN) AF: 0.0565 AC: 598 AN: 10576

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9644 AN: 67956

Other (OTH) AF: 0.178 AC: 375 AN: 2110

Alfa AF: 0.135 Hom.: 1149

Bravo AF: 0.211

TwinsUK AF: 0.176 AC: 652

ALSPAC AF: 0.164 AC: 633

ESP6500AA AF: 0.335 AC: 1478

ESP6500EA AF: 0.145 AC: 1247

ExAC AF: 0.140 AC: 17012

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.88
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.035	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.87	L
PhyloP100		0.78
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.048
Sift	Benign	0.27	T
Sift4G	Benign	0.20	T
Polyphen		0.046	B
Vest4		0.043
MutPred		0.49		Loss of phosphorylation at T50 (P = 0.0447)
MPC		0.090
ClinPred		0.0034	T
GERP RS		-1.0
Varity_R		0.072
gMVP		0.068
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs853678; hg19: chr6-28297313; COSMIC: COSV60181894; COSMIC: COSV60181894;