19-37698149-C-G

Variant names:

• chr19-37698149-C-G
• rs139379295
• NM_032689.5:c.1982G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032689.5(ZNF607):​c.1982G>C​(p.Ser661Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,782 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S661N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF607 NM_032689.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.93
• Publications: 3 publications found

Genes affected

ZNF607 (HGNC:28192): (zinc finger protein 607) 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]

ENSG00000267552 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042241663).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032689.5. 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
	ZNF607	NM_032689.5	MANE Select	c.1982G>C	p.Ser661Thr	missense	Exon 5 of 5	NP_116078.4
	ZNF607	NM_001172677.1		c.1979G>C	p.Ser660Thr	missense	Exon 5 of 5	NP_001166148.1	Q96SK3-3
	ZNF607	NM_001375895.1		c.1979G>C	p.Ser660Thr	missense	Exon 5 of 5	NP_001362824.1	Q96SK3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF607	ENST00000355202.9	TSL:2 MANE Select	c.1982G>C	p.Ser661Thr	missense	Exon 5 of 5	ENSP00000347338.2	Q96SK3-1
	ENSG00000267552	ENST00000586606.6	TSL:3	n.346+1636G>C		intron	N/A	ENSP00000467889.1	K7EQM0
	ZNF607	ENST00000920829.1		c.1982G>C	p.Ser661Thr	missense	Exon 5 of 5	ENSP00000590888.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251340 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461782 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727198

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111962

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.21
DANN	Benign	0.84
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.00089	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.12	N
PhyloP100		-5.9
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.020
Sift	Benign	1.0	T
Sift4G	Benign	0.64	T
Polyphen		0.0010	B
Vest4		0.057
MutPred		0.27		Gain of glycosylation at S661 (P = 0.0821)
MVP		0.12
MPC		0.046
ClinPred		0.047	T
GERP RS		-1.2
Varity_R		0.035
gMVP		0.011
Mutation Taster		=99/1	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: rs139379295; hg19: chr19-38189050;