chr6-27400587-G-A

Variant names:

• chr6-27400587-G-A
• rs200362306
• NM_001076781.3:c.217G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001076781.3(ZNF391):​c.217G>A​(p.Ala73Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000379 in 1,614,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: ZNF391 NM_001076781.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.91
• Publications: 7 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022429079).
• BP6: Variant 6-27400587-G-A is Benign according to our data. Variant chr6-27400587-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2347342.Status of the report is criteria_provided_single_submitter, 1 stars.

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.217G>A	p.Ala73Thr	missense	Exon 3 of 3	NP_001070249.1	Q9UJN7
	ZNF391	NM_001322288.2		c.217G>A	p.Ala73Thr	missense	Exon 4 of 4	NP_001309217.1	Q9UJN7
	ZNF391	NM_001322289.2		c.217G>A	p.Ala73Thr	missense	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.217G>A	p.Ala73Thr	missense	Exon 3 of 3	ENSP00000244576.4	Q9UJN7
	ZNF391	ENST00000901127.1		c.217G>A	p.Ala73Thr	missense	Exon 3 of 3	ENSP00000571186.1
	ZNF391	ENST00000901128.1		c.217G>A	p.Ala73Thr	missense	Exon 2 of 2	ENSP00000571187.1

Frequencies

GnomAD3 genomes AF: 0.000329 AC: 50 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000297 AC: 74 AN: 249318 AF XY: 0.000333

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000464

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000415

Gnomad OTH exome AF: 0.000496

GnomAD4 exome AF: 0.000384 AC: 562 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.000369 AC XY: 268 AN XY: 727228

African (AFR) AF: 0.0000896 AC: 3 AN: 33476

American (AMR) AF: 0.000470 AC: 21 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000301 AC: 26 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.000437 AC: 486 AN: 1111998

Other (OTH) AF: 0.000315 AC: 19 AN: 60394

GnomAD4 genome AF: 0.000328 AC: 50 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.000389 AC XY: 29 AN XY: 74470

African (AFR) AF: 0.0000481 AC: 2 AN: 41566

American (AMR) AF: 0.000523 AC: 8 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

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

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68030

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000414 Hom.: 0

Bravo AF: 0.000310

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000857 AC: 7

ExAC AF: 0.000273 AC: 33

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.091
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00070	N
LIST_S2	Benign	0.0034	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.46	N
PhyloP100		-1.9
PrimateAI	Benign	0.21	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.019
Sift	Benign	0.90	T
Sift4G	Benign	0.73	T
Polyphen		0.0	B
Vest4		0.012
MVP		0.072
MPC		0.13
ClinPred		0.0076	T
GERP RS		-2.1
Varity_R		0.021
gMVP		0.049
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: rs200362306; hg19: chr6-27368366; COSMIC: COSV55121870; COSMIC: COSV55121870;