11-33542780-T-C

Variant names:

• chr11-33542780-T-C
• rs761966574
• NM_012194.3:c.1217T>C

Variant summary

Our verdict is Likely benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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
• Publications: 0 publications found

Genes affected

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

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=0.05631441).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012194.3. 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
	KIAA1549L	NM_012194.3	MANE Select	c.1217T>C	p.Phe406Ser	missense	Exon 2 of 21	NP_036326.3	A0A590UJI0
	KIAA1549L	NM_001410965.1		c.583+634T>C		intron	N/A	NP_001397894.1	H0YDE5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1549L	ENST00000658780.2	MANE Select	c.1217T>C	p.Phe406Ser	missense	Exon 2 of 21	ENSP00000499430.1	A0A590UJI0
	KIAA1549L	ENST00000265654.6	TSL:2	c.449T>C	p.Phe150Ser	missense	Exon 1 of 11	ENSP00000265654.6	A0A5F9UK30
	KIAA1549L	ENST00000526400.7	TSL:5	c.583+634T>C		intron	N/A	ENSP00000433481.3	H0YDE5

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

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

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111816

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N
PhyloP100		0.80
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.019
Sift	Benign	0.29	T
Sift4G	Benign	0.20	T
Polyphen		0.041	B
Vest4		0.17
MutPred		0.38		Loss of stability (P = 0.0027)
MVP		0.085
MPC		0.30
ClinPred		0.034	T
GERP RS		0.098
PromoterAI		0.0081	Neutral
Varity_R		0.051
gMVP		0.10
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: rs761966574; hg19: chr11-33564326;