6-28995471-T-G

Variant names:

• chr6-28995471-T-G
• rs6456880
• NM_001382360.1:c.1531A>C

Variant summary

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

The NM_001382360.1(ZNF311):​c.1531A>C​(p.Lys511Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,613,784 control chromosomes in the GnomAD database, including 177,008 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.57 (28173 hom., cov: 32)
  • Exomes 𝑓: 0.44 (148835 hom.)
• Consequence: ZNF311 NM_001382360.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• Publications: 43 publications found

Genes affected

ZNF311 (HGNC:13847): (zinc finger protein 311) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

HCG15 (HGNC:18361): (HLA complex group 15)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=8.9732373E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382360.1. 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
	ZNF311	NM_001382360.1	MANE Select	c.1531A>C	p.Lys511Gln	missense	Exon 7 of 7	NP_001369289.1
	ZNF311	NM_001010877.5		c.1531A>C	p.Lys511Gln	missense	Exon 8 of 8	NP_001010877.2
	ZNF311	NM_001350637.4		c.1387A>C	p.Lys463Gln	missense	Exon 8 of 8	NP_001337566.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF311	ENST00000377179.4	TSL:5 MANE Select	c.1531A>C	p.Lys511Gln	missense	Exon 7 of 7	ENSP00000366384.3
	ZNF311	ENST00000483450.1	TSL:2	n.2341A>C		non_coding_transcript_exon	Exon 6 of 6
	HCG15	ENST00000716160.1		n.805-3651T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87013 AN: 151908 Hom.: 28110 Cov.: 32

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.603

GnomAD2 exomes AF: 0.504 AC: 125164 AN: 248516 AF XY: 0.499

Gnomad AFR exome AF: 0.891

Gnomad AMR exome AF: 0.523

Gnomad ASJ exome AF: 0.601

Gnomad EAS exome AF: 0.674

Gnomad FIN exome AF: 0.382

Gnomad NFE exome AF: 0.409

Gnomad OTH exome AF: 0.488

GnomAD4 exome AF: 0.439 AC: 642235 AN: 1461758 Hom.: 148835 Cov.: 69 AF XY: 0.443 AC XY: 322406 AN XY: 727176

African (AFR) AF: 0.898 AC: 30076 AN: 33480

American (AMR) AF: 0.532 AC: 23780 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 15555 AN: 26136

East Asian (EAS) AF: 0.611 AC: 24275 AN: 39700

South Asian (SAS) AF: 0.588 AC: 50677 AN: 86256

European-Finnish (FIN) AF: 0.386 AC: 20564 AN: 53326

Middle Eastern (MID) AF: 0.569 AC: 3283 AN: 5768

European-Non Finnish (NFE) AF: 0.400 AC: 445063 AN: 1111980

Other (OTH) AF: 0.480 AC: 28962 AN: 60390

GnomAD4 genome AF: 0.573 AC: 87123 AN: 152026 Hom.: 28173 Cov.: 32 AF XY: 0.574 AC XY: 42647 AN XY: 74302

African (AFR) AF: 0.882 AC: 36595 AN: 41500

American (AMR) AF: 0.557 AC: 8498 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2010 AN: 3468

East Asian (EAS) AF: 0.649 AC: 3337 AN: 5144

South Asian (SAS) AF: 0.608 AC: 2929 AN: 4816

European-Finnish (FIN) AF: 0.379 AC: 4009 AN: 10574

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27858 AN: 67948

Other (OTH) AF: 0.598 AC: 1261 AN: 2110

Alfa AF: 0.474 Hom.: 64123

Bravo AF: 0.605

TwinsUK AF: 0.392 AC: 1453

ALSPAC AF: 0.407 AC: 1568

ESP6500AA AF: 0.856 AC: 2586

ESP6500EA AF: 0.415 AC: 2247

ExAC AF: 0.507 AC: 61332

Asia WGS AF: 0.576 AC: 2004 AN: 3478

EpiCase AF: 0.416

EpiControl AF: 0.425

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.55
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0046	N
MetaRNN	Benign	9.0e-7	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.32
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.014
Sift	Benign	0.41	T
Sift4G	Benign	0.16	T
Polyphen		0.0	B
Vest4		0.013
MPC		0.20
ClinPred		0.00030	T
GERP RS		1.8
Varity_R		0.055
gMVP		0.020
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: rs6456880; hg19: chr6-28963248; COSMIC: COSV65852817;