rs140778870

Variant names:

• chr10-45626135-C-G
• NM_174890.4:c.1688G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-45626135-C-G
• chr10-45626135-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174890.4(ZFAND4):​c.1688G>C​(p.Cys563Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. C563Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZFAND4 NM_174890.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.61

Genes affected

ZFAND4 (HGNC:23504): (zinc finger AN1-type containing 4) Predicted to enable zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07207161).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAND4	NM_174890.4	c.1688G>C	p.Cys563Ser	missense_variant	Exon 7 of 10	ENST00000344646.10	NP_777550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAND4	ENST00000344646.10	c.1688G>C	p.Cys563Ser	missense_variant	Exon 7 of 10	1	NM_174890.4	ENSP00000339484.5
ZFAND4	ENST00000374366.7	c.1466G>C	p.Cys489Ser	missense_variant	Exon 8 of 11	1		ENSP00000363486.3
ZFAND4	ENST00000374371.6	c.570-7875G>C		intron_variant	Intron 5 of 6	5		ENSP00000363491.1
ZFAND4	ENST00000374370.1	n.1408G>C		non_coding_transcript_exon_variant	Exon 4 of 7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.31
DEOGEN2	Benign	0.00051	.;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.10	.;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.22	N;N
REVEL	Benign	0.14
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	.;B
Vest4		0.058
MutPred		0.76		.;Gain of disorder (P = 0.0059);
MVP		0.18
MPC		0.035
ClinPred		0.15	T
GERP RS		2.8
Varity_R		0.076
gMVP		0.17

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-46121583;