rs77238711

Variant names:

• chr19-30548762-C-T
• rs77238711
• NM_014717.3:c.3143C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-30548762-C-T
• chr19-30548762-C-A
• chr19-30548762-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014717.3(ZNF536):​c.3143C>T​(p.Ala1048Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 1,613,832 control chromosomes in the GnomAD database, including 1,508 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (135 hom., cov: 33)
  • Exomes 𝑓: 0.036 (1373 hom.)
• Consequence: ZNF536 NM_014717.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0720
• Publications: 14 publications found

Genes affected

ZNF536 (HGNC:29025): (zinc finger protein 536) The protein encoded by this gene is a highly conserved zinc finger protein. The encoded protein is most abundant in brain, where it negatively regulates neuronal differentiation. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017009676).
• BP6: Variant 19-30548762-C-T is Benign according to our data. Variant chr19-30548762-C-T is described in ClinVar as Benign. ClinVar VariationId is 403626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014717.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF536	NM_014717.3	MANE Select	c.3143C>T	p.Ala1048Val	missense	Exon 4 of 5	NP_055532.1	O15090
	ZNF536	NM_001376110.1		c.3143C>T	p.Ala1048Val	missense	Exon 5 of 6	NP_001363039.1	K7EQN6
	ZNF536	NM_001376111.1		c.3143C>T	p.Ala1048Val	missense	Exon 5 of 6	NP_001363040.1	K7EQN6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF536	ENST00000355537.4	TSL:1 MANE Select	c.3143C>T	p.Ala1048Val	missense	Exon 4 of 5	ENSP00000347730.1	O15090
	ZNF536	ENST00000592773.3	TSL:5	c.3143C>T	p.Ala1048Val	missense	Exon 5 of 6	ENSP00000467909.3	K7EQN6
	ZNF536	ENST00000706148.1		c.3143C>T	p.Ala1048Val	missense	Exon 5 of 7	ENSP00000516231.1	A0A994J7Z0

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5024 AN: 152096 Hom.: 135 Cov.: 33

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0228

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00368

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0200

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0352

Gnomad OTH AF: 0.0306

GnomAD2 exomes AF: 0.0364 AC: 9128 AN: 251030 AF XY: 0.0401

Gnomad AFR exome AF: 0.0340

Gnomad AMR exome AF: 0.0172

Gnomad ASJ exome AF: 0.0185

Gnomad EAS exome AF: 0.00315

Gnomad FIN exome AF: 0.0200

Gnomad NFE exome AF: 0.0321

Gnomad OTH exome AF: 0.0344

GnomAD4 exome AF: 0.0361 AC: 52831 AN: 1461618 Hom.: 1373 Cov.: 33 AF XY: 0.0382 AC XY: 27804 AN XY: 727084

African (AFR) AF: 0.0319 AC: 1067 AN: 33480

American (AMR) AF: 0.0179 AC: 802 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0188 AC: 492 AN: 26136

East Asian (EAS) AF: 0.00186 AC: 74 AN: 39700

South Asian (SAS) AF: 0.110 AC: 9507 AN: 86258

European-Finnish (FIN) AF: 0.0202 AC: 1072 AN: 53152

Middle Eastern (MID) AF: 0.0147 AC: 85 AN: 5768

European-Non Finnish (NFE) AF: 0.0339 AC: 37678 AN: 1112004

Other (OTH) AF: 0.0340 AC: 2054 AN: 60396

GnomAD4 genome AF: 0.0330 AC: 5024 AN: 152214 Hom.: 135 Cov.: 33 AF XY: 0.0338 AC XY: 2512 AN XY: 74422

African (AFR) AF: 0.0314 AC: 1303 AN: 41552

American (AMR) AF: 0.0227 AC: 347 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3472

East Asian (EAS) AF: 0.00349 AC: 18 AN: 5152

South Asian (SAS) AF: 0.121 AC: 585 AN: 4822

European-Finnish (FIN) AF: 0.0200 AC: 212 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0352 AC: 2395 AN: 67992

Other (OTH) AF: 0.0303 AC: 64 AN: 2112

Alfa AF: 0.0313 Hom.: 274

Bravo AF: 0.0297

TwinsUK AF: 0.0324 AC: 120

ALSPAC AF: 0.0324 AC: 125

ESP6500AA AF: 0.0365 AC: 161

ESP6500EA AF: 0.0335 AC: 288

ExAC AF: 0.0383 AC: 4653

Asia WGS AF: 0.0600 AC: 208 AN: 3478

EpiCase AF: 0.0322

EpiControl AF: 0.0317

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.7
DANN	Benign	0.89
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.072
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.025
Sift	Benign	0.12	T
Sift4G	Benign	0.11	T
Polyphen		0.0020	B
Vest4		0.022
MPC		0.12
ClinPred		0.0026	T
GERP RS		0.61
Varity_R		0.025
gMVP		0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs77238711; hg19: chr19-31039669; COSMIC: COSV62835849; COSMIC: COSV62835849;