19-51144580-C-T

Variant names:

• chr19-51144580-C-T
• rs373735842
• NM_014385.4:c.608C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014385.4(SIGLEC7):​c.608C>T​(p.Thr203Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,150 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T203N) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SIGLEC7 NM_014385.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31626058).

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.608C>T	p.Thr203Ile	missense	Exon 2 of 7	NP_055200.1	Q9Y286-1
	SIGLEC7	NM_016543.4		c.434-332C>T		intron	N/A	NP_057627.2	Q9Y286-2
	SIGLEC7	NM_001277201.2		c.433+1778C>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.608C>T	p.Thr203Ile	missense	Exon 2 of 7	ENSP00000323328.6	Q9Y286-1
	SIGLEC7	ENST00000305628.7	TSL:1	c.434-332C>T		intron	N/A	ENSP00000306757.6	Q9Y286-2
	SIGLEC7	ENST00000600577.1	TSL:1	c.433+1778C>T		intron	N/A	ENSP00000472529.1	Q9Y286-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152150 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74324

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2090

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	0.17
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.0074	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.84
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.033
Sift	Benign	0.10	T
Sift4G	Benign	0.14	T
Polyphen		0.87	P
Vest4		0.30
MutPred		0.42		Loss of glycosylation at T203 (P = 0.0328)
MVP		0.16
MPC		0.30
ClinPred		0.88	D
GERP RS		0.67
Varity_R		0.087
gMVP		0.24
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs373735842; hg19: chr19-51647837;