rs569347148

Variant names:

• chr3-102468964-C-G
• rs569347148
• NM_001329788.2:c.762C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-102468964-C-G
• chr3-102468964-C-T

Variant summary

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

The NM_001329788.2(ZPLD1):​c.762C>G​(p.Ser254Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S254S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZPLD1 NM_001329788.2 missense, splice_region
• Scores: Splicing: ADA: 0.001342
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.57
• Publications: 0 publications found

Genes affected

ZPLD1 (HGNC:27022): (zona pellucida like domain containing 1) Predicted to be an extracellular matrix structural constituent. Predicted to act upstream of or within vestibular reflex. Predicted to be located in cytoplasmic vesicle membrane. Predicted to be integral component of membrane. Predicted to be active in cell surface and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329788.2. 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
	ZPLD1	NM_001329788.2	MANE Select	c.762C>G	p.Ser254Arg	missense splice_region	Exon 9 of 12	NP_001316717.1	Q8TCW7-1
	ZPLD1	NM_175056.2		c.810C>G	p.Ser270Arg	missense splice_region	Exon 8 of 11	NP_778226.1	Q8TCW7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZPLD1	ENST00000466937.2	TSL:1 MANE Select	c.762C>G	p.Ser254Arg	missense splice_region	Exon 9 of 12	ENSP00000418253.1	Q8TCW7-1
	ZPLD1	ENST00000306176.5	TSL:1	c.810C>G	p.Ser270Arg	missense splice_region	Exon 8 of 11	ENSP00000307801.1	Q8TCW7-2
	ZPLD1	ENST00000491959.5	TSL:1	c.762C>G	p.Ser254Arg	missense splice_region	Exon 15 of 18	ENSP00000420265.1	Q8TCW7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.049
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.92	L
PhyloP100		2.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.44
Sift	Benign	0.096	T
Sift4G	Benign	0.32	T
Polyphen		0.015	B
Vest4		0.76
MutPred		0.66		Gain of catalytic residue at S254 (P = 0.023)
MVP		0.85
MPC		0.092
ClinPred		0.69	D
GERP RS		4.6
Varity_R		0.40
gMVP		0.68
Mutation Taster		=46/54	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0013
dbscSNV1_RF	Benign	0.12
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: rs569347148; hg19: chr3-102187808; COSMIC: COSV60355606;