19-37698548-C-G

Variant names:

• chr19-37698548-C-G
• rs150135894
• NM_032689.5:c.1583G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032689.5(ZNF607):​c.1583G>C​(p.Ser528Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,611,810 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: ZNF607 NM_032689.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.422
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012096196).

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.1583G>C	p.Ser528Thr	missense	Exon 5 of 5	NP_116078.4
	ZNF607	NM_001172677.1		c.1580G>C	p.Ser527Thr	missense	Exon 5 of 5	NP_001166148.1	Q96SK3-3
	ZNF607	NM_001375895.1		c.1580G>C	p.Ser527Thr	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.1583G>C	p.Ser528Thr	missense	Exon 5 of 5	ENSP00000347338.2	Q96SK3-1
	ENSG00000267552	ENST00000586606.6	TSL:3	n.346+1237G>C		intron	N/A	ENSP00000467889.1	K7EQM0
	ZNF607	ENST00000920829.1		c.1583G>C	p.Ser528Thr	missense	Exon 5 of 5	ENSP00000590888.1

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152028 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000123 AC: 31 AN: 251354 AF XY: 0.000162

Gnomad AFR exome AF: 0.0000615

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: 0.000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000227 AC: 331 AN: 1459782 Hom.: 0 Cov.: 71 AF XY: 0.000207 AC XY: 150 AN XY: 726178

African (AFR) AF: 0.0000598 AC: 2 AN: 33452

American (AMR) AF: 0.0000448 AC: 2 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26086

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000282 AC: 313 AN: 1110250

Other (OTH) AF: 0.000199 AC: 12 AN: 60312

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152028 Hom.: 0 Cov.: 32 AF XY: 0.000189 AC XY: 14 AN XY: 74264

African (AFR) AF: 0.0000725 AC: 3 AN: 41382

American (AMR) AF: 0.000197 AC: 3 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68022

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000325 Hom.: 0

Bravo AF: 0.000159

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000148 AC: 18

EpiCase AF: 0.000654

EpiControl AF: 0.000533

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	0.077
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.029
DANN	Benign	0.75
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.00082	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.46	N
PhyloP100		-0.42
PrimateAI	Benign	0.27	T
PROVEAN	Benign	3.5	N
REVEL	Benign	0.028
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0080	B
Vest4		0.076
MVP		0.088
MPC		0.047
ClinPred		0.019	T
GERP RS		-4.8
Varity_R		0.021
gMVP		0.0061
Mutation Taster		=98/2	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: rs150135894; hg19: chr19-38189449; COSMIC: COSV100778006; COSMIC: COSV100778006;