19-51144668-C-T

Variant names:

• chr19-51144668-C-T
• rs117714252
• NM_014385.4:c.696C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_014385.4(SIGLEC7):​c.696C>T​(p.Ile232Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 6.8e-7 (0 hom.)
• Consequence: SIGLEC7 NM_014385.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• Publications: 0 publications found

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]

ENSG00000268595 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.097058356).
• BP7: Synonymous conserved (PhyloP=-0.056 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014385.4. 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
	SIGLEC7	NM_014385.4	MANE Select	c.696C>T	p.Ile232Ile	synonymous	Exon 2 of 7	NP_055200.1	Q9Y286-1
	SIGLEC7	NM_016543.4		c.434-244C>T		intron	N/A	NP_057627.2	Q9Y286-2
	SIGLEC7	NM_001277201.2		c.433+1866C>T		intron	N/A	NP_001264130.1	Q9Y286-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC7	ENST00000317643.10	TSL:1 MANE Select	c.696C>T	p.Ile232Ile	synonymous	Exon 2 of 7	ENSP00000323328.6	Q9Y286-1
	SIGLEC7	ENST00000305628.7	TSL:1	c.434-244C>T		intron	N/A	ENSP00000306757.6	Q9Y286-2
	SIGLEC7	ENST00000600577.1	TSL:1	c.433+1866C>T		intron	N/A	ENSP00000472529.1	Q9Y286-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461240 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726948

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111914

Other (OTH) AF: 0.00 AC: 0 AN: 60378

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.2
DANN	Benign	0.66
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.097	T
PhyloP100		-0.056
Sift4G	Pathogenic	0.0	D
MVP		0.49
GERP RS		-5.5
Mutation Taster		=100/0	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: rs117714252; hg19: chr19-51647925; COSMIC: COSV58317811; COSMIC: COSV58317811;