6-37819982-A-T

Variant names:

• chr6-37819982-A-T
• rs1763629787
• NM_021943.3:c.37A>T

Variant summary

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

The NM_021943.3(ZFAND3):​c.37A>T​(p.Ser13Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,068,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: ZFAND3 NM_021943.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.53

Genes affected

ZFAND3 (HGNC:18019): (zinc finger AN1-type containing 3) Predicted to enable DNA binding activity and 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=0.2149325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAND3	NM_021943.3	c.37A>T	p.Ser13Cys	missense_variant	Exon 1 of 6	ENST00000287218.9	NP_068762.1
ZFAND3	NM_001410904.1	c.37A>T	p.Ser13Cys	missense_variant	Exon 1 of 5		NP_001397833.1
ZFAND3	XM_011514790.3	c.37A>T	p.Ser13Cys	missense_variant	Exon 1 of 5		XP_011513092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAND3	ENST00000287218.9	c.37A>T	p.Ser13Cys	missense_variant	Exon 1 of 6	1	NM_021943.3	ENSP00000287218.4
ZFAND3	ENST00000373391.6	c.37A>T	p.Ser13Cys	missense_variant	Exon 1 of 5	5		ENSP00000362489.2
ZFAND3	ENST00000474522.5	c.37A>T	p.Ser13Cys	missense_variant	Exon 1 of 6	5		ENSP00000420240.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000187 AC: 2 AN: 1068004 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 505242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000255

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 15, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.37A>T (p.S13C) alteration is located in exon 1 (coding exon 1) of the ZFAND3 gene. This alteration results from a A to T substitution at nucleotide position 37, causing the serine (S) at amino acid position 13 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	T;.;T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.096
Sift	Uncertain	0.026	D;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		0.98	D;.;.
Vest4		0.30
MutPred		0.24		Loss of glycosylation at S13 (P = 0.0309);Loss of glycosylation at S13 (P = 0.0309);Loss of glycosylation at S13 (P = 0.0309);
MVP		0.082
MPC		0.53
ClinPred		0.90	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.34

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

LitVar

Other links and lift over

dbSNP: rs1763629787; hg19: chr6-37787758;