rs761966574

Variant names:

• chr11-33542780-T-C
• NM_012194.3:c.1217T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-33542780-T-C
• chr11-33542780-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012194.3(KIAA1549L):​c.1217T>C​(p.Phe406Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. F406C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KIAA1549L NM_012194.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.804

Genes affected

KIAA1549L (HGNC:24836): (KIAA1549 like) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05631441).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1549L	NM_012194.3	c.1217T>C	p.Phe406Ser	missense_variant	Exon 2 of 21	ENST00000658780.2	NP_036326.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1549L	ENST00000658780.2	c.1217T>C	p.Phe406Ser	missense_variant	Exon 2 of 21		NM_012194.3	ENSP00000499430.1
KIAA1549L	ENST00000321505.9	c.326T>C	p.Phe109Ser	missense_variant	Exon 1 of 20	1		ENSP00000315295.4
KIAA1549L	ENST00000265654.6	c.449T>C	p.Phe150Ser	missense_variant	Exon 1 of 11	2		ENSP00000265654.6
KIAA1549L	ENST00000526400.7	c.583+634T>C		intron_variant	Intron 2 of 20	5		ENSP00000433481.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461578 Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1 AN XY: 727072

Gnomad4 AFR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.71
DEOGEN2	Benign	0.033	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.32	T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.056	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.97	N;N
REVEL	Benign	0.019
Sift	Benign	0.29	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.041	.;B
Vest4		0.17
MutPred		0.38		Loss of stability (P = 0.0027);Loss of stability (P = 0.0027);
MVP		0.085
MPC		0.30
ClinPred		0.034	T
GERP RS		0.098
Varity_R		0.051
gMVP		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-33564326;