6-27400586-C-T

Variant names:

• chr6-27400586-C-T
• rs61740694
• NM_001076781.3:c.216C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_001076781.3(ZNF391):​c.216C>T​(p.Asp72Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,614,172 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0091 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (20 hom.)
• Consequence: ZNF391 NM_001076781.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.17
• Publications: 2 publications found

Genes affected

ZNF391 (HGNC:18779): (zinc finger protein 391) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-4.17 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00906 (1380/152316) while in subpopulation AFR AF = 0.028 (1164/41558). AF 95% confidence interval is 0.0267. There are 22 homozygotes in GnomAd4. There are 608 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001076781.3. 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
	ZNF391	NM_001076781.3	MANE Select	c.216C>T	p.Asp72Asp	synonymous	Exon 3 of 3	NP_001070249.1	Q9UJN7
	ZNF391	NM_001322288.2		c.216C>T	p.Asp72Asp	synonymous	Exon 4 of 4	NP_001309217.1	Q9UJN7
	ZNF391	NM_001322289.2		c.216C>T	p.Asp72Asp	synonymous	Exon 4 of 4	NP_001309218.1	Q9UJN7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF391	ENST00000244576.9	TSL:2 MANE Select	c.216C>T	p.Asp72Asp	synonymous	Exon 3 of 3	ENSP00000244576.4	Q9UJN7
	ZNF391	ENST00000901127.1		c.216C>T	p.Asp72Asp	synonymous	Exon 3 of 3	ENSP00000571186.1
	ZNF391	ENST00000901128.1		c.216C>T	p.Asp72Asp	synonymous	Exon 2 of 2	ENSP00000571187.1

Frequencies

GnomAD3 genomes AF: 0.00907 AC: 1381 AN: 152198 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00903

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.00955

GnomAD2 exomes AF: 0.00334 AC: 832 AN: 249342 AF XY: 0.00275

Gnomad AFR exome AF: 0.0300

Gnomad AMR exome AF: 0.00690

Gnomad ASJ exome AF: 0.00228

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000795

Gnomad OTH exome AF: 0.00264

GnomAD4 exome AF: 0.00150 AC: 2192 AN: 1461856 Hom.: 20 Cov.: 31 AF XY: 0.00141 AC XY: 1025 AN XY: 727226

African (AFR) AF: 0.0270 AC: 903 AN: 33480

American (AMR) AF: 0.00707 AC: 316 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00218 AC: 57 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5768

European-Non Finnish (NFE) AF: 0.000647 AC: 719 AN: 1112002

Other (OTH) AF: 0.00295 AC: 178 AN: 60394

GnomAD4 genome AF: 0.00906 AC: 1380 AN: 152316 Hom.: 22 Cov.: 32 AF XY: 0.00816 AC XY: 608 AN XY: 74478

African (AFR) AF: 0.0280 AC: 1164 AN: 41558

American (AMR) AF: 0.00902 AC: 138 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000764 AC: 52 AN: 68036

Other (OTH) AF: 0.00945 AC: 20 AN: 2116

Alfa AF: 0.00350 Hom.: 3

Bravo AF: 0.0106

Asia WGS AF: 0.00202 AC: 8 AN: 3478

EpiCase AF: 0.00158

EpiControl AF: 0.000948

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.17
PhyloP100		-4.2
Mutation Taster		=100/0	polymorphism

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: rs61740694; hg19: chr6-27368365;