6-38116601-G-T

Variant names:

• chr6-38116601-G-T
• rs1210218675
• NM_021943.3:c.391G>T

Variant summary

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

The NM_021943.3(ZFAND3):​c.391G>T​(p.Val131Leu) variant causes a missense change. 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. V131I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFAND3 NM_021943.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.24
• Publications: 0 publications found

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

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=0.16019982).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021943.3. 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
	ZFAND3	NM_021943.3	MANE Select	c.391G>T	p.Val131Leu	missense	Exon 5 of 6	NP_068762.1	Q9H8U3
	ZFAND3	NM_001410904.1		c.325G>T	p.Val109Leu	missense	Exon 4 of 5	NP_001397833.1	E2QRF5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFAND3	ENST00000287218.9	TSL:1 MANE Select	c.391G>T	p.Val131Leu	missense	Exon 5 of 6	ENSP00000287218.4	Q9H8U3
	ZFAND3	ENST00000894325.1		c.418G>T	p.Val140Leu	missense	Exon 5 of 6	ENSP00000564384.1
	ZFAND3	ENST00000373391.6	TSL:5	c.325G>T	p.Val109Leu	missense	Exon 4 of 5	ENSP00000362489.2	E2QRF5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251246 AF XY: 0.00

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 Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.022
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		6.2
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.028
Sift	Benign	0.46	T
Sift4G	Benign	0.46	T
Polyphen		0.0080	B
Vest4		0.20
MutPred		0.26		Gain of solvent accessibility (P = 0.0086)
MVP		0.11
MPC		0.25
ClinPred		0.51	D
GERP RS		5.3
Varity_R		0.071
gMVP		0.14
Mutation Taster		=83/17	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: rs1210218675; hg19: chr6-38084377;