NM_174890.4:c.1973A>T

Variant names:

• chr10-45618215-T-A
• rs1465019972
• NM_174890.4:c.1973A>T

Variant summary

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

The NM_174890.4(ZFAND4):​c.1973A>T​(p.Gln658Leu) 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. 14/22 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. Q658R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFAND4 NM_174890.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.58
• Publications: 1 publications found

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

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=0.16754583).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174890.4. 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
	ZFAND4	NM_174890.4	MANE Select	c.1973A>T	p.Gln658Leu	missense	Exon 9 of 10	NP_777550.2	Q86XD8
	ZFAND4	NM_001128324.2		c.1973A>T	p.Gln658Leu	missense	Exon 9 of 10	NP_001121796.1	Q86XD8
	ZFAND4	NM_001282905.1		c.1751A>T	p.Gln584Leu	missense	Exon 10 of 11	NP_001269834.1	J3KPC0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFAND4	ENST00000344646.10	TSL:1 MANE Select	c.1973A>T	p.Gln658Leu	missense	Exon 9 of 10	ENSP00000339484.5	Q86XD8
	ZFAND4	ENST00000374366.7	TSL:1	c.1751A>T	p.Gln584Leu	missense	Exon 10 of 11	ENSP00000363486.3	J3KPC0
	ZFAND4	ENST00000947494.1		c.1991A>T	p.Gln664Leu	missense	Exon 9 of 10	ENSP00000617553.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.6
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.097
Sift	Uncertain	0.029	D
Sift4G	Benign	0.21	T
Polyphen		0.0050	B
Vest4		0.37
MutPred		0.27		Loss of solvent accessibility (P = 0.0217)
MVP		0.18
MPC		0.060
ClinPred		0.44	T
GERP RS		4.8
Varity_R		0.12
gMVP		0.34
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1465019972; hg19: chr10-46113663;