chr3-44594914-C-A

Variant names:

• chr3-44594914-C-A
• rs587776368
• NM_173658.4:c.721C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173658.4(ZNF660):​c.721C>A​(p.Arg241Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. R241C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF660 NM_173658.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40
• Publications: 0 publications found

Genes affected

ZNF660 (HGNC:26720): (zinc finger protein 660) This gene encodes a protein that contains multiple C2H2 zinc finger domains, and is located in a cluster of zinc-finger encoding genes on chromosome 3. Naturally-occurring readthrough transcription is observed between this gene and the downstream zinc finger protein 197 gene and is represented by GeneID:110354863. [provided by RefSeq, May 2017]

ZNF660-ZNF197 (HGNC:):

ZNF197 (HGNC:12988): (zinc finger protein 197) This gene product belongs to the zinc finger protein superfamily, members of which are regulatory proteins characterized by nucleic acid-binding zinc finger domains. The encoded protein contains 20 tandemly arrayed C2H2-type zinc fingers, a Kruppel-associated box (KRAB) domain, and a SCAN box. This transcript turns over rapidly and contains 3' UTR AUUUA motifs, which are often a hallmark of rapid turnover. It is overexpressed in some thyroid papillary carcinomas. This gene is located in a cluster of zinc finger genes at 3p21. Naturally-occurring readthrough transcription is observed between this gene and the upstream zinc finger protein 660 gene and is represented by GeneID:110354863. [provided by RefSeq, May 2017]

ZKSCAN7-AS1 (HGNC:53964): (ZKSCAN7 ZNF cluster antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.081781924).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173658.4. 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
	ZNF660	NM_173658.4	MANE Select	c.721C>A	p.Arg241Ser	missense	Exon 3 of 3	NP_775929.2	Q6AZW8
	ZNF660-ZNF197	NM_001351732.2		c.-82+8701C>A		intron	N/A	NP_001338661.1
	ZNF660-ZNF197	NM_001351733.2		c.-91+8701C>A		intron	N/A	NP_001338662.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF660	ENST00000322734.2	TSL:2 MANE Select	c.721C>A	p.Arg241Ser	missense	Exon 3 of 3	ENSP00000324605.2	Q6AZW8
	ZNF660	ENST00000853529.1		c.721C>A	p.Arg241Ser	missense	Exon 3 of 3	ENSP00000523588.1
	ZNF660	ENST00000913944.1		c.721C>A	p.Arg241Ser	missense	Exon 3 of 3	ENSP00000584003.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.065	N
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.61	N
PhyloP100		2.4
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.84	N
REVEL	Benign	0.094
Sift	Benign	0.089	T
Sift4G	Benign	0.072	T
Polyphen		0.0060	B
Vest4		0.27
MutPred		0.38		Loss of MoRF binding (P = 0.0338)
MVP		0.048
MPC		0.065
ClinPred		0.42	T
GERP RS		3.4
Varity_R		0.15
gMVP		0.039
Mutation Taster		=90/10	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: rs587776368; hg19: chr3-44636406;