NM_001205280.2:c.95C>T

Variant names:

• chr19-44613740-C-T
• rs918738344
• NM_001205280.2:c.95C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001205280.2(IGSF23):​c.95C>T​(p.Ala32Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,550,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A32E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: IGSF23 NM_001205280.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 1 publications found

Genes affected

IGSF23 (HGNC:40040): (immunoglobulin superfamily member 23) This gene encodes a protein that has one immunoglobulin (Ig) domain and is a member of the immunoglobulin superfamily. Proteins in this superfamily are usually found on or in cell membranes and act as receptors in immune response pathways. [provided by RefSeq, Nov 2011]

CEACAM22P (HGNC:):

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06072858).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205280.2. 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
	IGSF23	NM_001205280.2	MANE Select	c.95C>T	p.Ala32Val	missense	Exon 1 of 5	NP_001192209.1	A1L1A6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF23	ENST00000402988.6	TSL:3 MANE Select	c.95C>T	p.Ala32Val	missense	Exon 1 of 5	ENSP00000385592.1	A1L1A6
	IGSF23	ENST00000911252.1		c.95C>T	p.Ala32Val	missense	Exon 1 of 6	ENSP00000581311.1
	IGSF23	ENST00000911253.1		c.95C>T	p.Ala32Val	missense	Exon 1 of 3	ENSP00000581312.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000604 AC: 9 AN: 148942 AF XY: 0.0000748

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000407

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000185

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000157 AC: 22 AN: 1398240 Hom.: 0 Cov.: 33 AF XY: 0.0000174 AC XY: 12 AN XY: 689644

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.0000280 AC: 1 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.0000839 AC: 3 AN: 35736

South Asian (SAS) AF: 0.0000883 AC: 7 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.0000102 AC: 11 AN: 1078926

Other (OTH) AF: 0.00 AC: 0 AN: 57990

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152276 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74462

African (AFR) AF: 0.00 AC: 0 AN: 41562

American (AMR) AF: 0.0000653 AC: 1 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0077	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.25
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.60	N
REVEL	Benign	0.011
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.38	T
Vest4		0.11
MutPred		0.14		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.048
ClinPred		0.18	T
GERP RS		-0.0036
PromoterAI		0.051	Neutral
Varity_R		0.048
gMVP		0.081
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs918738344; hg19: chr19-45117050; COSMIC: COSV68806887; COSMIC: COSV68806887;