19-51142411-G-C

Variant names:

• chr19-51142411-G-C
• rs2092073929
• NM_014385.4:c.42G>C

Variant summary

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

The NM_014385.4(SIGLEC7):​c.42G>C​(p.Glu14Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: SIGLEC7 NM_014385.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.388

Genes affected

SIGLEC7 (HGNC:10876): (sialic acid binding Ig like lectin 7) Predicted to enable sialic acid binding activity. Predicted to be involved in cell adhesion. Predicted to be integral component of plasma membrane. Predicted to be active in plasma membrane. [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=0.11773223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC7	NM_014385.4	c.42G>C	p.Glu14Asp	missense_variant	Exon 1 of 7	ENST00000317643.10	NP_055200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC7	ENST00000317643.10	c.42G>C	p.Glu14Asp	missense_variant	Exon 1 of 7	1	NM_014385.4	ENSP00000323328.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1461816 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18 AN XY: 727210

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

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: 0.0000342

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.42G>C (p.E14D) alteration is located in exon 1 (coding exon 1) of the SIGLEC7 gene. This alteration results from a G to C substitution at nucleotide position 42, causing the glutamic acid (E) at amino acid position 14 to be replaced by an aspartic acid (D). 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	0.16
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.3
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	.;T;.;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.57	T;T;T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.6	.;N;N;.
REVEL	Benign	0.0050
Sift	Benign	0.045	.;D;D;.
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.024, 0.83, 0.94	.;B;P;P
Vest4		0.12, 0.077, 0.071
MutPred		0.37		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.44
MPC		0.14
ClinPred		0.13	T
GERP RS		1.3
Varity_R		0.11
gMVP		0.14

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: rs2092073929; hg19: chr19-51645668; COSMIC: COSV58318095; COSMIC: COSV58318095;