15-78880527-A-T

Variant names:

• chr15-78880527-A-T
• rs753870808
• NM_006791.4:c.103A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006791.4(MORF4L1):​c.103A>T​(p.Ile35Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,450,036 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. I35V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MORF4L1 NM_006791.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.84
• Publications: 0 publications found

Genes affected

MORF4L1 (HGNC:16989): (mortality factor 4 like 1) Enables protein N-terminus binding activity. Involved in double-strand break repair via homologous recombination and histone modification. Located in nuclear speck. Part of NuA4 histone acetyltransferase complex and Sin3 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2319358).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006791.4. 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
	MORF4L1	NM_006791.4	MANE Select	c.103A>T	p.Ile35Leu	missense	Exon 3 of 12	NP_006782.1	Q9UBU8-2
	MORF4L1	NM_206839.3		c.103A>T	p.Ile35Leu	missense	Exon 3 of 13	NP_996670.1	Q9UBU8-1
	MORF4L1	NM_001265604.2		c.-162A>T		5_prime_UTR	Exon 3 of 12	NP_001252533.1	Q9UBU8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORF4L1	ENST00000426013.7	TSL:1 MANE Select	c.103A>T	p.Ile35Leu	missense	Exon 3 of 12	ENSP00000408880.2	Q9UBU8-2
	MORF4L1	ENST00000331268.9	TSL:1	c.103A>T	p.Ile35Leu	missense	Exon 3 of 13	ENSP00000331310.5	Q9UBU8-1
	MORF4L1	ENST00000558893.5	TSL:1	n.148A>T		non_coding_transcript_exon	Exon 3 of 7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450036 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 721338

African (AFR) AF: 0.00 AC: 0 AN: 32912

American (AMR) AF: 0.00 AC: 0 AN: 42320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39438

South Asian (SAS) AF: 0.00 AC: 0 AN: 83456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5528

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107080

Other (OTH) AF: 0.0000167 AC: 1 AN: 59960

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.24
Eigen_PC	Benign	0.0091
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.71	N
PhyloP100		4.8
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.17
Sift	Benign	0.23	T
Sift4G	Benign	0.36	T
Polyphen		0.036	B
Vest4		0.35
MutPred		0.37		Loss of sheet (P = 0.0457)
MVP		0.53
MPC		0.67
ClinPred		0.53	D
GERP RS		5.6
Varity_R		0.49
gMVP		0.23
Mutation Taster		=32/68	disease causing

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: rs753870808; hg19: chr15-79172869;