NM_001321356.2:c.173G>A

Variant names:

• chr19-56458235-C-T
• rs149274211
• NM_001321356.2:c.173G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001321356.2(ZNF667):​c.173G>A​(p.Arg58Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,613,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: ZNF667 NM_001321356.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0280
• Publications: 0 publications found

Genes affected

ZNF667 (HGNC:28854): (zinc finger protein 667) Predicted to enable DNA-binding transcription factor activity 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07622054).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321356.2. 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
	ZNF667	NM_001321356.2	MANE Select	c.173G>A	p.Arg58Gln	missense	Exon 6 of 7	NP_001308285.1	Q5HYK9
	ZNF667	NM_022103.4		c.173G>A	p.Arg58Gln	missense	Exon 4 of 5	NP_071386.3
	ZNF667	NM_001321355.2		c.-100G>A		5_prime_UTR	Exon 4 of 6	NP_001308284.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF667	ENST00000504904.8	TSL:2 MANE Select	c.173G>A	p.Arg58Gln	missense	Exon 6 of 7	ENSP00000439402.1	Q5HYK9
	ZNF667	ENST00000292069.10	TSL:1	c.173G>A	p.Arg58Gln	missense	Exon 4 of 5	ENSP00000292069.5	Q5HYK9
	ZNF667	ENST00000909113.1		c.173G>A	p.Arg58Gln	missense	Exon 4 of 5	ENSP00000579172.1

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 152068 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000637 AC: 16 AN: 251364 AF XY: 0.0000810

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000376 AC: 55 AN: 1461706 Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28 AN XY: 727156

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.0000894 AC: 4 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1111902

Other (OTH) AF: 0.0000994 AC: 6 AN: 60376

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 152068 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74260

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.0000655 AC: 1 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000567

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000494 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.14
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.00069	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.24	N
PhyloP100		0.028
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.13
Sift	Benign	0.47	T
Sift4G	Uncertain	0.043	D
Polyphen		1.0	D
Vest4		0.38
MVP		0.34
MPC		0.55
ClinPred		0.14	T
GERP RS		4.0
Varity_R		0.045
gMVP		0.12
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs149274211; hg19: chr19-56969604; COSMIC: COSV99410595;